DISSERTATION RESEARCH: Impacts of metabolic differences on cytonuclear coevolution

生物体通过氧化磷酸化的代谢途径获取有机燃料以产生细胞能量。这个关键的过程是沿着一条相互作用的蛋白质链进行的，这条蛋白质链是由两个独立的基因组编码的，线粒体和细胞核，它们必须合作才能保持功能的完整性。能量需求水平直接影响这些代谢基因的分子进化。在鸟类中，与飞行相关的高能量需求与反映保守蛋白质功能的分子模式相关。动物之间存在着广泛的代谢需求，但这些差异对蛋白质进化的影响在很大程度上仍未被探索。蝾螈提供了一个独特的机会来研究代谢需求对分子进化的影响，因为它们的代谢需求极低，这使得它们比大多数其他脊椎动物能容忍更高水平的蛋白质变异。本研究将分析分子进化的模式，以确定必须维持蛋白质结构的哪些方面以保持代谢基因的功能完整性。这一目标将通过对几种蝾螈物种高度可变的线粒体和核基因组的大部分进行测序来实现。这项研究将对形成有氧代谢基础的核心蛋白质分子进化的力量进行全面分析。这些结果将提供对能量需求的分子基础的理解，这可能有助于理解与线粒体突变相关的遗传疾病的起源。通过本研究，将培养两名本科生和一名研究生在基因组学和生物信息学方面的研究。

Organisms harvest organic fuel to produce cellular energy through the metabolic pathway known as oxidative phosphorylation. This critical process is carried out along a chain of interacting proteins that are encoded by two separate genomes, mitochondrial and nuclear, that must cooperate to maintain functional integrity. Levels of energy demand directly impact the molecular evolution of these metabolic genes. In birds, the high energy demand associated with flight has been correlated with molecular patterns that reflect conserved protein function. There exists a wide range of metabolic demands across animals, but the impact of such differences on protein evolution remains largely unexplored. Salamanders provide a unique opportunity to examine the impacts of metabolic demand on molecular evolution due to their extremely low metabolic requirements, which allow them to tolerate higher levels of protein variation than most other vertebrates. This study will analyze patterns of molecular evolution to determine what aspects of protein structure must be maintained to retain functional integrity of metabolic genes. This goal will be met by sequencing large portions of the highly variable mitochondrial and nuclear genomes of several salamander species. This study will yield a comprehensive analysis of the forces shaping the molecular evolution of the core proteins underlying aerobic metabolism. These results will provide an understanding of the molecular underpinnings of energy demand, which may aid in understanding the origin of genetic diseases associated with mitochondrial mutations. Two undergraduates and one graduate student will be trained in genomics and bioinformatics through this research.